POS0405 TREATMENT WITH INTEGRIN Α10Β1-SELECTED MESENCHYMAL STEM CELLS ALLEVIATES POST-TRAUMATIC OSTEOARTHRITIS DEVELOPMENT IN AN EQUINE MODEL
Authors: C. Andersen, S. Jacobsen, K. Uvebrant, J. Griffin IV, L. Vonk, M. Walters, L. Berg, E. Lundgren-Åkerlund, C. Lindegaard
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Mesenchymal stem cells (MSCs) have gained much attention for their potential to treat osteoarthritis (OA) due to their regenerative and immunomodulatory properties. So far, studies have shown varying results, potentially due to variations in the MSC preparations. Previously it was shown that integrin α10β1-selected equine MSCs (integrin α10-MSCs) decrease cartilage degradation and bone sclerosis in an experimental equine post-traumatic OA model<sup>[1]</sup>, and that integrin α10β1-selected human MSCs could to home to experimental cartilage defects in rabbit knees and directly participate in new cartilage formation<sup>[2]</sup>. <h3>Objectives</h3> This study investigated disease modifying effects of integrin α10β1-selected MSCs in terms of joint function, cartilage structure and immunomodulation in an experimental equine post-traumatic OA model. <h3>Methods</h3> This was a non-randomized and partially blinded experimental study including 17 Standardbred trotters. OA was induced using the carpal osteochondral fragment model. On day 18 after surgery, the treatment-group (n = 8, all females) received 20x10<sup>6</sup> allogeneic adipose tissue-derived integrin α10-MSCs from a male equine donor. The control group was left untreated (n = 9). From day 14 after surgery and until study termination on day 70, the horses underwent weekly joint and lameness examinations (AAEP score and flexion tests) and synovial fluid collection. After euthanasia, the carpi were evaluated by computed tomography (CT), magnetic resonance imaging (MRI), macroscopic pathology and histology evaluation. MSCs were traced through PCR detection of the Y-chromosome in the cell pellet from the synovial fluid samples and in tissue samples from cartilage, synovial membrane, and subchondral bone from the osteochondral fragment site, collected postmortem. <h3>Results</h3> A significant improvement of lameness scores (<i>p</i>=0.02) and response to flexion (<i>p</i>=0.004) over time was observed in the treatment group, while the untreated group had no change in lameness and a smaller decrease in flexion response (<i>p</i>=0.03). No joint flares were seen after MSC treatment. The integrin α10-MSCs treated horses had significantly less macroscopic cartilage pathology (<i>p</i>=0.019), lower cartilage histology score (<i>p</i>=0.037) and showed a better but not statistically significant (<i>p</i>=0.069) healing of the osteochondral fragment on CT. Prostaglandin E2 (PGE2) and interleukin-10 (IL-10) were significantly increased in the synovial fluid of the treated group on day 21 (<i>p</i>=0.018 and <i>p</i>=0.035, resp) and on day 28 (<i>p</i>=0.0606 and <i>p</i>=0.042, resp) compared to day 18. Interleukin-6 (IL-6) showed a non-significant increase in the treated group on day 21 (<i>p</i>=0.085). MSCs were detected in the synovial fluid of the treated horses on day 21 (n=8), day 28 (n=1) and day 35 (n=2) and in the cartilage/subchondral bone (n=7) at study termination (day 70), which was 52 days after integrin α10-MSC treatment. <h3>Conclusion</h3> Intra-articular injection of integrin α10-MSCs is safe, alleviates the development of pathological changes in the joint and improves joint function in an equine post-traumatic OA model. In addition, integrin α10-MSCs were still present in the joint 52 days after treatment. This suggests that that integrin α10-MSCs hold potential to be a disease modifying treatment of OA. <h3>References</h3> [1]Delco, M. L. <i>et al.</i> Integrin α10β1-Selected Mesenchymal Stem Cells Mitigate the Progression of Osteoarthritis in an Equine Talar Impact Model. <i>Am. J. Sports Med.</i><b>48</b>, 612–623 (2020). [2]Andersen, C. <i>et al.</i> Human integrin α10β1-selected mesenchymal stem cells home to cartilage defects in the rabbit knee and assume a chondrocyte-like phenotype. <i>Stem Cell Res. Ther.</i><b>13</b>, 1–15 (2022). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Camilla Andersen Employee of: C.A. is an employee of Xintela AB, Stine Jacobsen: None declared, Kristina Uvebrant Shareholder of: K.U. holds stock in Xintela AB, Employee of: K.U. is an employee of Xintela AB, John Griffin IV: None declared, Lucienne Vonk Grant/research support from: Not related to this study: L.V. has received research grants from Smith&amp;Nephew, Arthrex and Ivy Sports Medicine (Stryker) in the past, Employee of: Not related to this study: L.V. was an employee of CO.DON AG. Related: L.V. is employed by Xintela AB, Marie Walters: None declared, Lise Berg: None declared, Evy Lundgren-Åkerlund Shareholder of: E.L.Å. holds stock in Xintela AB, Employee of: E.L.Å. is CEO and CSO of Xintela AB, Casper Lindegaard: None declared.